Dilactide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1998-06-23 to 1998-08-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted March 1996

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 30 september 1996

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(3S-cis)-3,6-dimethyl-1,4-dioxane-2,5-dione

EC Number:

224-832-0

EC Name:

(3S-cis)-3,6-dimethyl-1,4-dioxane-2,5-dione

Cas Number:

4511-42-6

Molecular formula:

C6H8O4

IUPAC Name:

(3S,6S)-3,6-dimethyl-1,4-dioxane-2,5-dione

Specific details on test material used for the study:

- Batch no.: DA 778 FN
- Purity: >99.5%
- Labelling: L-lactide
- Bulk density: 0.8 kg/L
- Package: sealed plastic bags
- General appearance: white crystalline powder
- Storage conditions: at ca. -20 °C.

Test animals

Species:

rat

Strain:

other: Crl:(WI) WU BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

Males and females, 5-6 weeks old upon arrival, were individually ear marked. A maximum of five animals per cage (stainless steel cages, fitted with wire-screen floor and front). Lighting was a 12 hours light / 12 hours dark cycle. Temperature: 22 ± 3 °C. Humidity: 54-87.5% (upper limit higher than 70%, because of meteorological circumstances and/or wet cleaning of the animal room). Ventilation was ca. 10 air changes/hour. Animals were fed standard laboratory rodent diet ad libitum. Each batch of this diet was analyzed by the supplier (SDS Special Diets services, Whitham, England) for the nutrients and contaminants and the results are available upon request. Tap water (N.V. Waterleidingbedrijf Midden-Nederland) ad libitum. Results of routine physical, chemical and microbiological examination of drinking water as conducted by the supplier are available upon request.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The study was started with treatment of three females with a 2000 mg/kg body weight dose level. Since all females survived the first 3 days after treatment, it was decided to continue treatment with 3 males dosed with the 2000 mg/kg dose level. The animals were dosed with a 10 mL/kg b.w. dosing-volume of a 200 mg/mL dilution of the test substance in maize oil to obtain the 2000 mg/kg dose level.
The exact amount of the test substance to be dosed was calculated for each animal individually and administered by means of a syringe, equipped with an oral gavage. Prior to dosing, the animals had fasted overnight. Approximately four hours after dosing, they had access to food again. The animals were observed for mortality up to 14 days after treatment.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: All visible reactions to treatment were recorded, including type, severity, onset and duration. Observations were made within 1 hour and within 4 hours after dosing, and subsequently at least once daily throughout the observation period. The body weight of each animal was recorded immediately before dosing on day 0, and of the surviving animals on days 3, 7 and 14 of the study.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology. At the end of the observation period, on day 14 of the study, all surviving animals were killed with carbon dioxide and examined for external changes. Next, the abdomen and the thorax of each animal was opened and examined for gross pathological changes.

Statistics:

N.A.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: None

Body weight:

other body weight observations

Remarks:

No adverse effects on body weight

Gross pathology:

Examination at autopsy of the males and females did not reveal treatment-related gross alterations.

Applicant's summary and conclusion

Interpretation of results:

other: CLP criteria not met

Conclusions:

Since no mortality occurred during the 14-day observation period, the LD50 of L-lactide exceeds 2000 mg/kg bw in both male and female rats. Therefore, L-lactide is considered not harmful after oral ingestion.

Executive summary:

In an acute oral toxicity study conducted according to OECD guideline 423, a group of male and female Wistar outbred rats; Crl:(WI) WU BRA (n = 3/sex) were given a single oral dose of L-lactide (purity > 99.5%) at a dose level of 2000 mg/kg body weight.

No mortality or distinct clinical signs were observed after treatment. Macroscopic examination of the animals at the end of the observation period did not reveal any treatment-related gross changes. Since no mortality occurred during the 14-day observation period, the acute oral LD50 of L-lactide is considered to exceed 2000 mg/kg body weight, in both male and female rats. L-lactide is considered to be not harmful after oral ingestion.